Journal article
Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline
Neurology, Vol.89(21), pp.2176-2186
11/21/2017
DOI: 10.1212/WNL.0000000000004670
PMCID: PMC5696639
PMID: 29070667
Abstract
To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline.
Amyloid-positive participants with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSp
], limbic predominant [LP
], typical AD [tAD
]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models.
When participants were divided categorically, the HpSp
group showed significantly more AD-like hypometabolism on
F-fluorodeoxyglucose-PET (
< 0.05) and poorer baseline executive function (
< 0.001). Other baseline clinical measures did not differ across the 3 groups. Participants with HpSp
also showed faster subsequent clinical decline than participants with LP
on the Alzheimer's Disease Assessment Scale, 13-Item Subscale (ADAS-Cog
), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all
< 0.05) and tAD
on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both
< 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog
score (
< 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy.
AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation.
Details
- Title: Subtitle
- Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline
- Creators
- Shannon L Risacher - From the Department of Radiology and Imaging Sciences (S.L.R., A.J. Saykin, A.J. Schwarz), Indiana Alzheimer Disease Center (S.L.R., A.J. Saykin), and Department of Biostatistics (P.F.C.), Indiana University School of Medicine; Eli Lilly and Company (W.H.A., A.C., S.S., A.J. Schwarz), Indianapolis; and Department of Psychological and Brain Sciences (A.J. Schwarz), Indiana University, BloomingtonWesley H Anderson - From the Department of Radiology and Imaging Sciences (S.L.R., A.J. Saykin, A.J. Schwarz), Indiana Alzheimer Disease Center (S.L.R., A.J. Saykin), and Department of Biostatistics (P.F.C.), Indiana University School of Medicine; Eli Lilly and Company (W.H.A., A.C., S.S., A.J. Schwarz), Indianapolis; and Department of Psychological and Brain Sciences (A.J. Schwarz), Indiana University, BloomingtonArnaud Charil - From the Department of Radiology and Imaging Sciences (S.L.R., A.J. Saykin, A.J. Schwarz), Indiana Alzheimer Disease Center (S.L.R., A.J. Saykin), and Department of Biostatistics (P.F.C.), Indiana University School of Medicine; Eli Lilly and Company (W.H.A., A.C., S.S., A.J. Schwarz), Indianapolis; and Department of Psychological and Brain Sciences (A.J. Schwarz), Indiana University, BloomingtonPeter F Castelluccio - From the Department of Radiology and Imaging Sciences (S.L.R., A.J. Saykin, A.J. Schwarz), Indiana Alzheimer Disease Center (S.L.R., A.J. Saykin), and Department of Biostatistics (P.F.C.), Indiana University School of Medicine; Eli Lilly and Company (W.H.A., A.C., S.S., A.J. Schwarz), Indianapolis; and Department of Psychological and Brain Sciences (A.J. Schwarz), Indiana University, BloomingtonSergey Shcherbinin - From the Department of Radiology and Imaging Sciences (S.L.R., A.J. Saykin, A.J. Schwarz), Indiana Alzheimer Disease Center (S.L.R., A.J. Saykin), and Department of Biostatistics (P.F.C.), Indiana University School of Medicine; Eli Lilly and Company (W.H.A., A.C., S.S., A.J. Schwarz), Indianapolis; and Department of Psychological and Brain Sciences (A.J. Schwarz), Indiana University, BloomingtonAndrew J Saykin - From the Department of Radiology and Imaging Sciences (S.L.R., A.J. Saykin, A.J. Schwarz), Indiana Alzheimer Disease Center (S.L.R., A.J. Saykin), and Department of Biostatistics (P.F.C.), Indiana University School of Medicine; Eli Lilly and Company (W.H.A., A.C., S.S., A.J. Schwarz), Indianapolis; and Department of Psychological and Brain Sciences (A.J. Schwarz), Indiana University, Bloomington. asaykin@iupui.edu a.schwarz@lilly.comAdam J Schwarz - From the Department of Radiology and Imaging Sciences (S.L.R., A.J. Saykin, A.J. Schwarz), Indiana Alzheimer Disease Center (S.L.R., A.J. Saykin), and Department of Biostatistics (P.F.C.), Indiana University School of Medicine; Eli Lilly and Company (W.H.A., A.C., S.S., A.J. Schwarz), Indianapolis; and Department of Psychological and Brain Sciences (A.J. Schwarz), Indiana University, Bloomington. asaykin@iupui.edu a.schwarz@lilly.comAlzheimer's Disease Neuroimaging Initiative
- Contributors
- Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.89(21), pp.2176-2186
- Publisher
- United States
- DOI
- 10.1212/WNL.0000000000004670
- PMID
- 29070667
- PMCID
- PMC5696639
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Grant note
- K01 AG049050 / NIA NIH HHS P30 AG010129 / NIA NIH HHS P41 EB015922 / NIBIB NIH HHS R01 AG054076 / NIA NIH HHS
- Language
- English
- Date published
- 11/21/2017
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984051768602771
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